Letermovir Prophylaxis in Children With EBV-Positive T/NK-Cell Lymphoproliferative Disease and Refractory/Relapsed EBV-Associated Hemophagocytic Lymphohistiocytosis

• Letermovir (Drug): Arm 1 (Letermovir Prophylaxis): Pediatric patients receive oral letermovir once daily from day 0 to day 100 post-transplant. Prophylaxis may be extended to day 200 if high-risk factors persist (steroid use, poor immune reconstitution). Dosing: 480mg (≥30kg), 240mg (15-30kg), 120mg (7.5-15kg), 80mg (6-7.5kg); halved if co-administered with cyclosporine. Arm 2 (Control): Historical control cohort (2018-2023) receiving no routine CMV prophylaxis; preemptive therapy with ganciclovir/foscarnet initiated only when plasma PCR exceeds threshold.

Primary outcomes

• Incidence of Clinically Significant CMV Infection (cs-CMVi) and EBV Infection (cs-EBVi) [Up to 180 days and 360 days post-transplant]: To evaluate the incidence of clinically significant CMV and EBV infections in pediatric patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with or without letermovir prophylaxis.

Secondary outcomes

• Incidence of Other Viral Infections and Transplant-Related Complications [Up to 100, 180, 270, and 360 days post-transplant]: To assess the incidence of other viral infections (e.g., BKV, HHV-6/7, RSV, ADV, HSV), graft-versus-host disease (GvHD), post-transplant lymphoproliferative disorder (PTLD), thrombotic microangiopathy (TMA), graft failure, relapse, overall survival (OS), and immune reconstitution (T/B/NK cell counts and function).

Other outcomes

• Safety and Tolerability of Letermovir in Pediatric allo-HSCT Recipients [From initiation of letermovir (Day 0-28 post-transplant) until 30 days after discontinuation (up to approximately 360 days post-transplant)]: To monitor adverse events (AEs) and serious adverse events (SAEs) related to letermovir prophylaxis, including gastrointestinal symptoms, liver function abnormalities, cardiac events, and other treatment-emergent AEs.

Sex: All, ages: any to 18 Years

Inclusion Criteria:

* Diagnosed with EBV-positive T/NK lymphoproliferative disease (EBV-T/NK LPD) according to ICC 2022 criteria, or diagnosed with refractory/relapsed EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) according to the 2004-HLH diagnostic criteria;
* Undergoing first allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the study center;
* Age < 18 years;
* CMV seropositive (IgG+) prior to transplantation;
* Presence of at least one high-risk factor for CMV infection: haploidentical transplantation, HLA-mismatched transplantation, receipt of ATG (including ATLG/ALG) in conditioning, sustained corticosteroid use post-conditioning, donor/recipient CMV serostatus mismatch, or positive NGS result pre-transplant.

Exclusion Criteria:

* History of CMV end-organ disease within 6 months prior to enrollment;
* Severe hepatic dysfunction (defined as Child-Pugh Class C);
* End-stage renal impairment with creatinine clearance < 10 mL/min (calculated by Cockcroft-Gault equation);
* Prior allogeneic hematopoietic stem cell transplantation;
* Expected survival ≤ 3 months;
* Received radiation therapy during conditioning;
* Initiation of letermovir prophylaxis after day 28 post-transplant;
* Letermovir dosage or administration not in accordance with the prescribing information;
* Lack of signed informed consent.